It is well known that L-carnitine and its alkanoyl derivatives lend themselves to various therapeutical and nutritional uses. L-Carnitine and its alkanoyl derivatives inner salts are represented by formula:
wherein R represents either a hydrogen atom or an alkanoyl group.
L-Carnitine is a cofactor required for transformation of free long-chain fatty acids into acylcarnitines, and for their subsequent transport into the mitochondrial matrix, where they undergo bate-oxidation for cellular energy production. Mitochondrial fatty oxidation is the primary fuel source in heart and skeletal muscles, pointing to the relative importance of the nutrient for proper function in tissue. L-Carnitine and its alkanoyl derivatives also have important antioxidant effects, as demonstrated by their protective effect against lipoperoxidation of phospholipid cell membranes caused by oxidative stress induced at the myocardial and endothelial cell level. Conditions which appear to benefit from L-carnitine and its alkanoyl derivatives include anorexia, chronic fatigue, coronary vascular disease, diphtheria, hypoglycemia, male infertility, muscular myopathies, Rett Syndrome, Alzheimer's disease, mood enhancement, cognitive improvement, and sports performance. See, e.g., Gregory S. Kelly, “L-Carnitine: Therapeutic Applications of a Conditionally-Essential Amino Acid”, Alternative Medicine Review, 3 (5): 345-360 (1998).
While there are various therapeuticals and nutritional benefits of L-carnitine and its alkanoyl derivatives, much research has been carried out to improve their physical, chemical, and biological properties.
Research has primarily focused on the solutions of the physical and chemical drawbacks of L-carnitine and its alkanoyl derivatives inner salts because their hygroscopic physical characteristic creates complex problems involving the processing and storing of both the raw materials and the finished products, and their inadequate chemical stability leads to the release of traces of trimethylamine and its concomitant unpleasant fishy smell.
In these previous research, various salt forms of L-carnitine and its alkanoyl derivatives having “pharmacologically acceptable” acids as anion but without unwanted toxic or side effects have been produced, with the knowledge that the salts of L-carnitine and its alkanoyl derivates known to-date present the same therapeutical and nutritional benefits as do the so-called inner salts. Selecting suitable acid is the major endeavor in screening salt forms of L-carnitine and its alkanoyl derivatives having improved properties compared to inner salts. While various mineral acids have been tested, including hydrochloric acid, sulfuric acid, phosphoric acid, a larger number of organic acids have been tested including fumaric acid, tartaric acid, lactic acid, citric acid, malic acid, oxalic acid, orotic acid and mucic acid. While the combination of these acids with the inner salts of L-carnitine and its alkanoyl derivatives more or less satisfactorily solved the problems associated with inner salts, these salts focused on a technological solution to the purely physical or chemical drawbacks associated with L-carnitine and its alkanoyl derivatives' inner salts.
Research has been made to produce salt forms of L-carnitine and its alkanoyl derivatives with the anion moiety itself being endowed with interesting pharmacological and/or nutritional characteristics and, if possible, to synergistically enhance the therapeutical and/or nutritional properties of L-carnitine and its alkanoyl derivatives.
U.S. Patent Application Publication, No. US2006/0241181 A1 entitled “Alpha-Ketoglutarates of Active Ingredients and Compositions Containing Same” (Publication Date: Oct. 26, 2006) to Pietro Pola et al. discloses novel salt forms of L-carnitine and its alkanoyl derivatives combined with alpha-ketoglutaric acid. Alpha-ketoglutaric acid, which is a precursor to L-glutamine, plays an important metabolic role and has been successfully applied in cardiac surgery due to its important role in the Krebs cycle and, hence, in myocardial metabolism. However, according to the specification of this patent application, only honey-like pasty mass is obtained as a salt product of L-carnitine alpha-ketoglutarate and not any solid form.
Amino acids possess various therapeutical and nutritional attributes. U.S. Pat. No. 6,703,042 B1, entitled “Salts of L-Carnitine and Lower Alkanoyl L-Carnitine”, (Issued: Mar. 9, 2004) to Atonietta Buononato discloses salts of L-carnitine and alkanoyl L-carnitine with amino acids, such as leucine, isoleucine, valine, cysteine, arginine and glycine to enhance therapeutical and/or nutritional efficacy with respect to their inner salts. However, as disclosed in this patent, the anion moiety (i.e., the amino acid moiety) of the salts had to be salified at the amino group with hydrochloric, or hydrobromic, and/or phosphoric acid.
In the efforts to develop new generation salt forms of L-carnitine and alkanoyl L-carnitines which not only just solve the physical and chemical drawbacks of the inner salts, but also enhance the therapeutical and/or nutritional efficacy of the inner salts, endeavors should still focus on the screening of a sophisticated acid.
Phytic acid, also known as inositol hexaphosphate, myo-inositol hexaphosphate, and IP6, is a 6-phosphate ester of inositol as represented by the molecular formula:

Phytic acid is naturally occurring in substantial amounts in whole grain, cereals, legumes, nuts, and seeds, and is the primary energy source for germinating plants. Phytic acid and its lower phosphorylated forms are also found in most mammalian cells, where they assist in regulating a variety of important cellular functions. Phytic acid functions as an antioxidant by chelating divalent cations such as copper and iron, preventing the generation of reactive oxygen species responsible for cell injury and carcinogenesis. Both in vivo and in vitro studies utilizing IP6 have revealed a significant anticancer activity with a variety of tumor types, possibly via inhibition of tumor cell growth and differentiation. In vitro studies with colon, liver, and rhabdomyosarcoma cell lines, and animal models of mammary, colon, intestinal, and liver cancer, as well as rhabdomyosarcoma, have all demonstrated IP6's anticancer properties. Other properties of IP6 include an anti-platelet aggregating and lipid-lowering effect, suggesting a potential health benefit for the cardiovascular system; inhibition of HIV-1 virus replication; modulation of insulin secretion in pancreatic beta cells; and inhibition of urinary calcium oxalate crystallization, thereby preventing renal stone development. See e.g. Monograph, “Inositol Hexaphosphate”, Alternative Medicine Review, 7 (3): 244-248 (2002).
Other notable functions of phytic acid include the deodorant effect of body odor, bad breath or uraroma; the prevention of acute alcoholism; and the enrichment of the taste of meat and fish. These properties of phytic acid provide its pharmaceutical and/or nutritional added value.
The biochemistry and pharmacokinetics of phytic acid have also been studied. Inositol phosphates are synthesized from the parent molecule inositol and daily dietary consumption of inositol is estimated to be one gram. Once inositol reaches the cells of the intestinal tract it is phosphorylated to create inositol hexaphosphate (IP6), and then subsequently dephosphorylated to its lower forms, such as inositol pentaphosphate (IP5), inositol tetraphosphate (P4), inositol triphosphate (IP3), inositol monophosphate (IP1), which play important roles in signal transduction. Independent of the route of administration, IP6 has been discovered to be absorbed almost instantly, transported intracellularly and dephosphorylted into lower inositol phosphates. IP6 can reach targeted tumor tissue as early as one hour post-administration. When incubated with a human mammary cancer cell line, low levels of IP6 were detected as early as one minute post-incubation.
Based on its dietary derivation (i.e., it is non-toxic), its chemical properties (e.g., six phosphates attached in one inositol molecule), and its various biological activities, phytic acid is a novel acid to react with L-carnitine and alkanoyl L-carnitine inner salts to produce L-carnitine phytate and alkanoyl L-carnitine phytates. It is apparently an innovation in the evolution of salt forms of L-carnitine and salt forms of alkanoyl L-carnitine.